icon-    folder.gif   Conference Reports for NATAP  
  20th Conference on Retroviruses and
Opportunistic Infections
Atlanta, GA March 3 - 6, 2013
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Impact of Interleukin 7 and Raltegravir plus Maraviroc intensification on total HIV DNA reservoir: Results from ERAMUNE 01
  Reported by Jules Levin
CROI 2013
Christine Katlama1, Sidonie Lambert-Niclot2, Lambert Assoumou3, Laura Papagno4, Francois Lecardonnel4, Giuseppe Tambussi5, Bonaventura Clotet6, Mike Youle7, Dominique Costagliola3, Brigitte Autran8 and the EraMune-01 Study Group
1Department of Infectious and Tropical Diseases, Pitie-Salpetriere Hospital, Paris; 2Laboratory of Virology, UPMC/INSERM UMR-S943, Paris; 3Center of Methodology, UPMC/INSERM UMR-S943, Paris; 4ORVACS; 5Vaccine and Immunotherapy Research Center, San Raffaele Hospital, Milan; 6HIV Unit, Hospital Universitari Germans Trias i Pujol, Badalona; 7Ian Charleson Day Center, Royal Free Hospital Hampstead, London; 8Laboratory of Cellular and Tissular Immunology, UPMC/INSERM UMR-S945


Abstract #: D-1003
Background: Potential strategies aiming at purging the HIV reservoirs such as interleukin-7 shown to reactivate latent HIV in CD4 lymphocytes combined with dual intensification with integrase and CCR5 inhibitors deserve clinical investigation.
Methods: ERAMUNE-01 was a randomized, non-comparative screening trial. CART-treated patients with plasma HIV-RNA<50 cp/ ml, CD4 >350/mm3 and HIV-DNA between 10 to 1,000 copies/106 PBMCs) were randomized 1:1 after 8 weeks of RAL/MVC intensification to receive 3 injections of r-hIL-7 at W8-W9-W10 (RAL/MVC/IL7 arm) or to maintain intensification alone (RAL/MVC arm). As in oncology phase 2 trials, at least one response, defined as a decrease in HIV-DNA >0.5 logs at Week 56, should be observed out of 14 evaluable patients for the intervention to be further considered.
Results: A total of 29 patients were enrolled (15 in RAL/MVC/IL7 and 14 in RAL/MVC arms). They had a median 615 CD4 cells/ mm3, 348 HIV-DNA cp/106 PBMCs and viral suppression duration of 2.3 years.
No decrease in HIV reservoir was observed in any patient. No change in HIV-DNA occurred in the RAL/MVC arm along the 56 weeks. In contrast, the mean cell-associated HIV-DNA/106 PBMC increased transiently at W12, after IL-7 injections, (∼W12-D0=532 cp, p=0.001) but did not differ from baseline value at W56 (∼W56-D0=161 cp, p=0.088).
The estimated HIV-DNA cp/106 CD4 cells levels followed the same dynamics, though less pronounced, while the mean HIV-DNA cp/mL whole blood remained higher both at W12 (∼W12-D0= 5194 cp/mL, p=0.002) and W56 (∼W56-D0=1446 cp/mL, p=0.001). These HIV-DNA dynamics paralleled the 3.5-fold increase in CD4 cells (D0: 606 cells/mm3, W12: 2,127 cells/mm3, p=0.001) that remained significantly higher at W56 (975 cells/mm3, p=0.001). This change in CD4 count consisted in a durable increase in the proportion of central-memory cells (TCM, ∼W56-D0=6.5%, p=0.001) while other subsets remained stable or decreased. Nonetheless, contrasting with the overall increase in CD4 and CD8 counts, both CD4 and CD8 cell activation and immune-senescence markers decreased.
Conclusions: Intensification with maraviroc plus raltegravir with or without IL7 was not able to decrease the total HIV-DNA reservoir in peripheral blood cells. Whether the massive CD4 cell proliferation induced by IL-7 could have masked the reactivation of HIV transcription from some latently infected cells targeted by IL-7 is currently further investigated.